• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

(Norwegian) Wyller: Kronisk utmattelsessyndrom/ME – sykdomsmekanismer, diagnostik...

mango

Senior Member
Messages
905
(Not a recommendation.)

Tidsskr Nor Legeforen - Publisert først på nett 1. desember 2015
doi: 10.4045/tidsskr.15.1180

Kronikk
Kronisk utmattelsessyndrom/myalgisk encefalopati – sykdomsmekanismer, diagnostikk og behandling

V B Wyller S E Reme T E Mollnes 

Ved kronisk utmattelsessyndrom/myalgisk encefalopati (CFS/ME) er det uavklarte underliggende sykdomsmekanismer og faglig uenighet om diagnosekriterier og behandlingsmetoder. Her gjennomgår vi forskningslitteraturen og kommenterer også debatten omkring tilstanden.

Kronisk utmattelsessyndrom/myalgisk encefalopati (CFS/ME) er en alminnelig – og alvorlig – tilstand karakterisert av gjennomgripende utmattelse (spesielt i etterkant av bagatellmessige anstrengelser) og kroniske smerter samt konsentrasjons- og hukommelsesproblemer (1).

Continue reading:
http://tidsskriftet.no/article/3426100
 

Sidereal

Senior Member
Messages
4,856
Scary:

We believe the evidence base for cognitive behavioral therapy is so solid that all patients with chronic fatigue syndrome / myalgic encephalopathy should be offered such treatment. The sickest patients are often bedridden in a darkened room. Over time, this can have serious bodily and mental consequences (45, 46). We therefore believe that CBT also should be attempted in this subgroup, although the documentation is poor. The minimal adverse risk suggests that failing to treat the most severely ill patients is riskier than providing such treatment.
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
That man is so full of C*** and contradictions. Doesn`t even spell Rituximab right.

He demands evidence for everything else than his own theory. Bizarre.

And of course he don`t mention the phase two-trial or the ongoing phase 3-trial. The agenda is sickening.
When I get well I shall illuminate his nonsense for the public to see.
For the time being I hope some Norwegian doctors step up for the task.

Or maybe we could get James Coyne on the case?
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253

It really is. It*s so important that somebody replies to this article. I`ve already contacted a few. Iv`e also sent some e-mails to Wyller with questions, but he don`t answer, as he don`t have any answers..
 

Gijs

Senior Member
Messages
690
He has disapproved his own theory
http://www.consultant360.com/story/clonidine-doesnt-help-adolescents-chronic-fatigue

That said i agree with Wyller that an abnormal stressrespons is a key problem in ME/CFS but not due to psychologial stress. There is something very wrong with our ANS/HPA or it is a compensation respons. Very dangerous to put this system down if you don't know the cause. Dr. Bansal has found glucocorticoïd resistance which could explain this problem very well!
 
Last edited:

Cheshire

Senior Member
Messages
1,129
He tried twice to put his theory into practise, using clonidine with adolescents. He failed twice.

Disease mechanisms and clonidine treatment in adolescent chronic fatigue syndrome: a combined cross-sectional and randomized clinical trial.

Sulheim D1, Fagermoen E2, Winger A3, Andersen AM4, Godang K5, Müller F6, Rowe PC7, Saul JP8, Skovlund E9, Øie MG10, Wyller VB11.

JAMA Pediatr. 2014


Main Outcomes and Measures Number of steps per day.

Results At baseline, patients with CFS had a lower number of steps per day (P < .001), digit span backward score (P = .002), and urinary cortisol to creatinine ratio (P = .001), and a higher fatigue score (P < .001), heart rate responsiveness (P = .02), plasma norepinephrine level (P < .001), and serum C-reactive protein concentration (P  = .04) compared with healthy controls. There were no significant differences regarding blood microbiology evaluation. During intervention, the clonidine group had a lower number of steps per day (mean difference, −637 steps; P = .07), lower plasma norepinephrine level (mean difference, −42 pg/mL; P = .01), and lower serum C-reactive protein concentration (mean ratio, 0.69; P = .02) compared with the CFS placebo group


http://archpedi.jamanetwork.com/article.aspx?articleid=1827799

Effects of low-dose clonidine on cardiovascular and autonomic variables in adolescents with chronic fatigue: a randomized controlled trial.
Fagermoen E, Sulheim D, Winger A, Andersen AM, Gjerstad J, Godang K, Rowe PC, Saul JP, Skovlund E, Wyller VB.
BMC Pediatr.
2015

A central feature of CFS is orthostatic intolerance and abnormal autonomic cardiovascular control characterized by sympathetic predominance. We hypothesized that symptoms as well as the underlying pathophysiology might improve by treatment with the alpha2A-adrenoceptor agonist clonidine.

Low-dose clonidine reduces catecholamine levels in adolescent CFS, but the effects on autonomic cardiovascular control are sparse. Clonidine does not improve symptoms of orthostatic intolerance.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4566847/pdf/12887_2015_Article_428.pdf
 
Messages
2,087
He has disapproved his own theory
http://www.consultant360.com/story/clonidine-doesnt-help-adolescents-chronic-fatigue

That said i agree with Wyller that an abnormal stressrespons is a key problem in ME/CFS but not due to psychologial stress. There is something very wrong with our ANS/HPA or it is a compensation respons. Very dangerous to put this system down if you don't know the cause. Dr. Bansal has found glucocorticoïd resistance which could explain this problem very well!

Is it abnormal to have a stress response to these articles ?
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
He disapprove his own theory
http://www.consultant360.com/story/clonidine-doesnt-help-adolescents-chronic-fatigue

That said i agree with Wyller that an abnormal stressrespons is a key problem in ME/CFS but not due to psychologial stress. There is something very wrong with our ANS/HPA or it is a compensation respons. Very dangerous to put this system down if you don't know the cause. Dr. Bansal has found glucocorticoïd resistance which could explain this problem very well!
Is it abnormal to have a stress response to these articles ?

Hah! Maybe he will stop publishing articles if we convince him that he is contributing to our sustained stressresponse..
 

Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
Dr. Bansal has found glucocorticoïd resistance which could explain this problem very well!

Glucocorticoid resistance has not been found in most ME/CFS patients, in fact there are suggestions of increased GC receptor affinity or expression, based on the evidence so far, though most studies had results more on the normal side.

Most of the claims of 'stress' problems in ME/CFS are not credible based on the evidence.
 
Last edited:

A.B.

Senior Member
Messages
3,780
Glucocorticoid resistance has not been found in most ME/CFS patients, in fact there are suggestions of increased GC receptor affinity or expression, based on the evidence so far.

Anecdotally, I reacted strongly to an ACTH stimulation test, suggesting sensitive receptors.

A trend towards lower than average cortisol levels is also consistent with increased receptor sensitivity (less cortisol needed to acheive the same effect).

Again anecdotally, in every day life it also seems to be that there is tendency to react strongly to stressful events, but there is no sustained stress response. Relapses produce symptoms that can't be explained by a stress response alone.

In my case catecholamines in urine, in particular norepinephrine, were very low. I believe this contradicts Wyller's theory. Side note: does anyone know what very low norepinephrine in urine actually means?

I think the body might be doing this on purpose to get us to avoid the stressors that can trigger relapses.
 

A.B.

Senior Member
Messages
3,780
This may seem strange, but on a psychological level, many patients (non severe) actually have lower day to day stresses compared to someone working full time and this may explain the subtle shifts you have observed.

Or maybe it's really this simple. My life is very boring and uneventful for the most part.
 

biophile

Places I'd rather be.
Messages
8,977
We believe the evidence base for cognitive behavioral therapy is so solid that all patients with chronic fatigue syndrome / myalgic encephalopathy should be offered such treatment. The sickest patients are often bedridden in a darkened room. Over time, this can have serious bodily and mental consequences (45, 46). We therefore believe that CBT also should be attempted in this subgroup, although the documentation is poor. The minimal adverse risk suggests that failing to treat the most severely ill patients is riskier than providing such treatment.

There's plenty of room on the BPS Titanic for those who refuse to see the icebergs. There's no convincing safety data for severely affected patients, and the safety is disputable even for the moderately affected. There's also evidence from trials that CBT does not increase activity levels, so the idea that patients can safely increase activity levels is unsupported by evidence.
 

Gijs

Senior Member
Messages
690
I believe that many patients have a wrong idea about stress. Wyller thinks psychological factors maintains a chronic stress response. This idea is outdated and objectively wrong. Nevertheless, in ME there is a sustained abnormal sympathetic activity, especially after physical and mental exertion This is a very important objective and measurable phenomenon with huge consequences. PEM is the distinguishing symptom of ME.
 
Messages
15,786
In my case catecholamines in urine, in particular norepinephrine, were very low. I believe this contradicts Wyller's theory. Side note: does anyone know what very low norepinephrine in urine actually means?
I tested low for norepinephrine in urine as well, and later tests in blood were even lower. And NRI (Strattera) and then Yohimbe have both helped with my OI problems, probably by boosting norepinephrine levels and/or making existing amounts more effective.
 

mango

Senior Member
Messages
905
When I get well I shall illuminate his nonsense for the public to see.
For the time being I hope some Norwegian doctors step up for the task.

Or maybe we could get James Coyne on the case?

i was just reading through some comments in the facebook group "Norges ME-forening - voksne" and it seems ME-foreningen (the norwegian ME association) and possibly their scientific council are on the case. i guess we'll just have to wait and see...
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Glucocorticoid resistance has not been found in most ME/CFS patients, in fact there are suggestions of increased GC receptor affinity or expression, based on the evidence so far, though most studies had results more on the normal side.
The finding by Bansal is in fact an increase of a glucocorticoid receptor, if I recall correctly the beta receptor. This receptor inhibits the glucocorticoid response because it is an inactive receptor, presumably evolved as a control mechanism to prevent excessive glucocorticoid responses. However this research needs much more work and a decent article published. Until that happens we cannot be sure of its importance, or indeed if it can be replicated.
 

Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
The finding by Bansal is in fact an increase of a glucocorticoid receptor, if I recall correctly the beta receptor. This receptor inhibits the glucocorticoid response because it is an inactive receptor, presumably evolved as a control mechanism to prevent excessive glucocorticoid responses. However this research needs much more work and a decent article published. Until that happens we cannot be sure of its importance, or indeed if it can be replicated.

That still contradicts some of the current evidence, which suggested either normal or slightly increased (not decreased) GR response to agonists.
 

mango

Senior Member
Messages
905
I'm cross posting this here and in the thread for the English version of the same article.

A comment by Saugstad has been published now :thumbsup:

(See below for the Google translated version)

RE: Kronisk utmattelsessyndrom/myalgisk encefalopati - sykdomsmekanismer, diagnostikk og behandling

22.12.2015

Bruun Wyller og medarbeidere oppsummerer i Tidsskriftet sin forståelse av myalgisk encefalopati (ME) som en vedvarende stressrespons (1). Kronikken må forstås som en kommentar til Egeland og medarbeidere om ME hvor vi oppsummerer internasjonal status for sykdomsforståelsen (2). Den største synteserapporten som foreligger, fra Institute of Medicine i USA, slår klart fast at ME er en biomedisinsk sykdom (3). Det er denne rapporten Bruun Wyller og medarbeidere burde kommentere hvis de er uenig i konklusjonene våre, i stedet for å bruke flere avsnitt på å karakterisere andre deltagere i ME debatten. Rapporten kan sees som et oppgjør med bl.a. Bruun Wyllers syn på ME.

Bruun Wyllers gjennomgang av litteraturen er mangelfull. En ny studie av Horning og medarbeidere viser at cytokinprofilen endres over tid med sykdomsforløpet til ME-pasienter. (4). I Bruun Wyllers egen studie og den refererte meta-analysen er denne tidsfaktoren utelatt. En fersk studie viser at isolerte muskelceller fra ME pasienter responderer annerledes på fysisk stress enn friske kontroller, blant annet ved å ikke ta opp glukose (5). Nylig påviste Loebel og medarbeidere (6) forhøyede antistoffer i serum mot β-adrenerge og muskarin-kolinerge reseptorer hos ME pasienter. Og hvorfor ønsker Bruun Wyller å tone ned betydningen av den lovende Rituximab studien på Haukeland, som trekker i retning av at ME er en autoimmun sykdom?

Studiene om effekten av kognitiv adferdsterapi ved ME er lite overbevisende. PACE studien, som Bruun Wyller oftest refererer til, viser ikke at kognitiv adferdsterapi har bedre effekt enn andre behandlinger, inkludert aktivitetstilpasning. Ved for eksempel 6 min gangtest gir kognitiv adferdsterapi behandling en økning på 20 meter i forhold til aktivitetstilpasning, men fortsatt er pasientgruppen på et svært lavt funksjonsnivå (7). Det er i tillegg en rekke alvorlige metodiske svakheter med PACE studien. I tillegg rapporterer mange pasienter at de blir dårligere av kognitiv adferdsterapi.

Bruun Wyller og medarbeidere misliker at noen ”i vitenskapelige toppstillinger uttaler seg med skråsikkerhet om et fagområde de verken har klinisk eller vitenskapelig erfaring fra”. Jeg har engasjert meg for ME pasientene fordi jeg har sett hvor dårlig mange av dem behandles. Jeg har i flere år reist rundt i hele landet og besøkt mange av de sykeste pasientene hjemme eller på sykehjem. Mange av dem faller utenfor helsevesenets tilbud. Jeg har jevnlig deltatt på internasjonale ME kongresser de siste 20 årene.

Bruun Wyller og medarbeideres syn på ME representerer gårsdagens forståelse og er slik sett av liten interesse. Problemet er at denne forståelsen har bidratt til manglende utredning og dårlige og misforståtte behandlinger av svært syke pasienter.

Litteratur
1. Wyller VB, Reme SE, Mollnes TE. Kronisk utmattelsesyndrom/Myalgisk encepalopati-sykdomsmemanismer, diagnostikk og behandling. Tidsskr Nor Laegeforen. 2015;135(23-24):2172-2175
2. Egeland T, Angelsen A, Haug R, Henriksen JO, Lea TE, Saugstad OD. Hva er egentlig Myaligisk encepalopati? Tidsskr Nor Laegeforen. 2015;135:1756-1759
3. Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Board on the Health of Select Populations, Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press (US); 2015 Feb 10. http://iom.edu/~/media/Files/Report% 20Files/2015/MECFS/MECFS_ReportBrief.pdf (2.9. 2015).
4. Hornig M, Montoya JG, Klimas NG et al. Distinct plasma immune signatures in ME/CFS are present early in the course of illness. Sci Adv 2015; 1: e1400121.
5. Brown AE, Jones DE, Walker M et al. Abnormalities of AMPK Activation and glucose uptake in cultured skeletal muscle cells from individuals with chronic fatigue syndrome. Plos One 2015; 19; e0122982.
6. Loebel M, Grabowski P, Heidecke H, Bauer S, Hanitsch LG, Wittke K, et al. Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome. Brain Behav Immun. 2015: S0889-1591(15)30020-9.
7. White PD, Goldsmith KA, Johnson AL et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377: 823 – 36

Professor Ola Didrik Saugstad

Pediatrisk Forskningsinstitutt, UiO og OUS

Oppgitte interessekonflikter: ingen

Here's the Google Translate version:
RE: Chronic fatigue syndrome / myalgic encephalomyelitis - pathophysiology, diagnosis and treatment

12/22/2015

Bruun Wyller and colleagues summarize the journal's understanding of myalgic encephalomyelitis (ME) as a sustained stress response (1). The article must be understood as a comment on Egeland and colleagues about ME where we summarize international status of disease understanding (2). The main synthesis report that has been presented by the Institute of Medicine in the United States, clearly states that ME is a biomedical disease (3). It is this report Bruun Wyller and employees should comment if they disagree with our conclusions, instead of using several paragraphs to characterize other participants in ME debate. The report can be seen as a showdown with ia Bruun Wyller views on ME.

Bruun Wyller review of the literature is lacking. A new study of Horning and colleagues show that cytokine profiles change over time with the disease to ME patients. (4). In Bruun Wyller own study and the referenced meta-analysis is the time factor omitted. A recent study shows that muscle cells isolated from ME patients respond differently to physical stress than healthy controls, including by not absorb glucose (5). Recently discovered Loebel and colleagues (6) elevated antibodies in serum against β-adrenergic and muscarinic cholinergic receptors in ME patients. And why would Bruun Wyller to downplay the importance of the promising Rituximab study at Haukeland, which suggests that ME is an autoimmune disease?

The studies on the effect of cognitive behavioral therapy in ME is unconvincing. PACE study, that Bruun Wyller most often refers to, does not show that cognitive behavioral therapy is more effective than other treatments, including activity adaptation. For example, 6 min walk test provide cognitive behavioral therapy treatment an increase of 20 meters relative to activity adaptation, but still patient population at a very low level of functioning (7). There are in addition a number of serious methodological weaknesses with PACE study. In addition, reports many patients that they become poorer of cognitive behavioral therapy.

Bruun Wyller and employees resent that someone "in top academic positions makes statements with absolute certainty about a subject they have neither clinical or scientific experience." I have engaged me for ME patients because I have seen how poorly many of them treated. I have for several years traveled around the country and visited many of the sickest patients at home or in nursing homes. Many of them fall outside the healthcare offerings. I have regularly participated in international congresses ME the last 20 years.

Bruun Wyller and employees' views on ME represents yesterday's understanding and as such is of little interest. The problem is that this understanding has contributed to a lack of investigation and bad and misguided treatments of very ill patients.

http://tidsskriftet.no/article/3431709#comments
 
Last edited: